NEUROPSYCHOPHARMACOLOGIC STUDIES OF MARIJUANA: SOME SYNTHETIC AND NATURAL THC DERIVATIVES IN ANIMALS AND MAN*

Abstract

One of the tasks of a pharmacologist is the classification of drugs. Marijuana and its derivatives pose some problems. Legally marijuana has been classified as a narcotic, yet pharmacologically it is quite different. Mankind has known about the Cannabis plant from which marijuana and other products are obtained for more than 4,708 years. A considerable body of data is available to describe its gross effects. Over the centuries it has been called a depressant, euphoriant, inebriant, intoxicant, hallucinogen, psychotomimetic, sedative-hypnotic-anesthetic, and stimulant. Perhaps more than any other drug it is a social irritant that elicits rather remarkable behavior reactions in both users and nonusers. Moreau’ in 1845, employed it to produce a model psychosis, thus initiating the fashion to study hallucinogens as a means of gaining insights into mental illness. Lewin2 classified Cannabis as one of the “phantastica: hallucinating substances.” One text on hallucinogens3 does not even refer to Cannabis, but another does? There are some aspects of the subjective effects of both LSD-25 and Cannabis that are similar, yet the latter produces sedative effects, no significant sympathomimetic actions, and no cross-tolerance to LSD-25. Hollister5 reviewed the recent findings on the effects in man of marijuana and its putative active ingredient Ag-THC, stressing that current investigators have, for the most part, confirmed the Cannabis-induced clinical syndromes long known to occur. New knowledge of the active ingredients, biotransformation, dosage, pharmacokinetics, tolerance, and cross-tolerance in animals and man is now rapidly accumulating, thanks to the medicinal chemists who have provided us with relatively pure compounds (see Mechoulama). Yet for all the reading one may do about marijuana, there is nothing like the experience of personal research. This paper describes some of those experiences done first in the 1950s and later in the 1960-70s in animals and, subsequ-ntly, in man. The issue of classification is implicit in the attempt to ask what marijuana or its pure active derivatives do to various brain functions. Where and how do they act, using those limited techniques available in one’s own laboratory? This research is due to the efforts of many of my students or associates whose work has been or is being published in separate form in the near future.